Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis

Angiogenesis, formation of new vessels from pre-existing ones, results from stimulation of endothelial cells, which line the vessel wall. These cells will leave their resting state and start to digest the basement membrane, p roliferate, migrate and eventually differentiate to form a hollow tube. All these steps can be induced by growth factors and this review will focus on two important types of angiogenic growth factors, vascular endothelial gro wth factor (VEGF; also denoted vascular permeability factor, VPF) and fibro blast growth factor (FGF). Both types of factors bind to cell surface expre ssed receptors, which are ligand-stimulatable tyrosine kinases. Binding of the growth factors to their receptors leads to activation of the intrinsic tyrosine kinase and signal transduction to downstream signalling cascades. This results in transcriptional changes and biological responses. The molec ular aspects of signalling cascades critical for endothelial cell prolifera tion and migration are beginning to be delineated. In contrast, signalling cascades leading to endothelial cell differentiation remain to be determine d. Angiogenesis is essential for a number of physiological events such as e mbryonic development, ovulation, and wound healing. It has become increasin gly clear that a number of diseases depend on angiogenesis. For future deve lopment of therapeutic tools, it is important to understand the molecular m echanisms that regulate angiogenesis. (C) 2000 Elsevier Science Ireland Ltd . All rights reserved.